Statins and Tendinopathy

[asdf]

Does anyone know of a consensus statement regarding statins and tendon issues? Particularly in people who engage in high-intensity exercise, like heavy resistance training, Olympic weightlifting, sprints, long trail runs, box jumps, etc.

Is this an issue on which you’ve done a deep dive, @Austin or @JordanFeigenbaum ? Do you think it's worth worrying about?

I’ll post conclusions from ten journal articles below. The research is divided. I don’t know enough to judge the quality of the competing studies, so I’m hoping that a trustworthy individual or group has a done a careful review and reached a conclusion. If anyone has personal experience, I'd love to hear about that as well.

[asdf]

<< Association or Increased Risk >>

2012 Summary published in Muscle, Ligaments, and Tendons Journal
Statins have adverse effects on the tendon. Statins may increase the risk of tendon rupture by altering matrix metalloproteinases activity (8). Adverse effects of statins mainly occurred during the first year of treatment and appeared to be more frequent in patients with diabetes, hyperuricaemia or a history of tendon disorders, and in persons engaging in strenuous sports (9).

2016 Review in The Journal of Bone and Joint Surgery
Use of statins may be associated with certain tendinopathies and tendon ruptures, especially of the Achilles, quadriceps, and distal biceps tendons.

2017 Lab experiment published in PLOS ONE
In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.

2019 cohort study combined with an experimental study in the journal Scientific Reports
In conclusion, statin use appears to be associated with a higher risk of developing tendinopathy, in both men and women. We suspect that this adverse effect might be linked to an excessive MMP release followed by a weakened tendon matrix.
 
2021 Retrospective study published in The Journal of Hand Surgery
After statistical analysis, it was found nearly two times more likely to have spontaneous distal biceps tendon rupture with use of statins. Based on the results of our study we conclude that there is a trend of association of spontaneous distal biceps tendon ruptures with statin administration.

2023 Cohort study published in Orthopaedic Journal of Sports Medicine
This nationwide population-based cohort study suggests that statin use regardless of the statin type was associated with a greater risk of tendinopathy compared with that of nonusers. The risk of tendinopathy development was diluted with the increasing cumulative defined daily dose. If a patient is going to have issues with tendinopathy from statin use, it will likely manifest in the first 180 days of use.

<< No Association or Increased Risk >>

2009 Case-control study published in The Journal of Cardiovascular Pharmacology
In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins.

2016 Sytematic review in The Medical Journal of Australia
On the basis of the limited data available, tendon rupture while using statin therapy is an infrequent occurrence, and one high-quality study demonstrated that event rates were no different to the background rate in the general population. Indeed, two high-quality cohort studies provided strong evidence that simvastatin reduces the risk of tendinopathy. There is limited evidence for causality between statin therapy and tendon rupture.

2016 Propensity Score-Matched Sequential Cohort Study published in the journal Drug Safety
The results of this cohort study suggest that statin use does not increase the risk of tendon rupture, irrespective of gender, age, statin dose, or treatment duration.
 
2018 Study comparing Achilles tendon structures in statin-user vs. non published in PLOS ONE
These findings demonstrate that there is no evidence of a negative statin influence on Achilles tendon structure. Given earlier reports that the risk of Achilles injury is equivalent in statin users and non-users, weightbearing exercise may be prescribed without placing the Achilles tendon at a higher risk of injury than among the general population. The results of this study are consistent with the known negative effects of elevated BMI on tendon structure, suggesting that an assessment of the Achilles tendons prior to prescribing weightbearing exercise may be prudent in obese individuals.

[Austin]

Hey -

I am aware of this being a frequent topic of discussion, although I have not done a deep dive into it myself. The risk is plausible, however there are also other considerations - for example, we also know that hyperlipidemia/dyslipidemia (and other metabolic disorders) can drive changes in tendon structure & function, too. This makes it tricky to figure things out from these kinds of retrospective and other observational study designs.

So while I find the relationship plausible, the risk is likely to be very low, as well as dose-dependent (and may also vary between different statins). However, I don't think it's helpful to discuss these kinds of risks or relationships in overly general/broad terms, compared with discussing things in the context of an individual person's cardiovascular risk. There are often alternative medication management strategies to address someone's blood lipids & overall risk in the face of perceived adverse effects.

[asdf]

Thanks for your response, @Austin. Much appreciated.

Thanks as well for your excellent, informative Guide to Cholesterol articles. They (along with the citations therein) helped me wade through the quagmire of assessing both cardiovascular and treatment risks.